| Theme |
New aspect of calcium, magnesium and phosphate transport -- Basic principles and clinical applications |
| Title |
Roles of megalin in renal phosphate reabsorption |
| Author |
Toshimi Michigami |
Department of Environmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health |
| [ Summary ] |
Phosphate homeostasis is maintained mainly by the control of phosphate excretion in the kidnies. Urinary excretion of phosphate is regulated by the reabsorption via sodium / phosphate co-transporters type II a and II c (NaPi-II a, NaPi-II c) localized in the brush border membrane (BBM) in the proximal tubules. Megalin is a multifunctional endocytic receptor expressed in BBM. It is involved in the endocytosis of various ligands, including 25-hydroxyvitamin D / vitamin D binding protein complex and parathyroid hormone (PTH). In kidney specific megalin knockout mice, it has been reported that steady state levels of NaPi-II a in BBM are enhanced and urinary excretion of phosphate is reduced. In another mouse model where the soluble form of receptor-associated protein (RAP) was administered, the endocytosis of megalin was accelerated. This accelaration was associated with the internalization of NaPi-II a and increased urinary excretion of phosphates. These findings suggest a functional linkage between megalin and phosphate reabsorption in the proximal tubules. |